Project description
Microbiome-fibroblast crosstalk in the intestine
The bacteria, fungi and other microorganisms living in our intestine, known as microbiota, are known to play a key role in intestinal immunity. However, the underlying mechanisms remain unclear. Intestinal fibroblasts (iFBs), originally considered to be structural cells, are now emerging as key immune regulators capable of directly sensing microbial signals. With the support of the Marie Skłodowska-Curie Actions programme, the FibroBiomeCrosstalk project aims to investigate how the crosstalk between the microbiome and iFBs shapes immunity during development, homeostasis and inflammation. Researchers will undertake single cell and spatial transcriptomic analysis to identify microbial sensing pathways in iFBs and determine their role in inflammatory bowel disease (IBD). Project findings have the potential to guide future strategies for IBD management.
Objective
The microbiome plays an essential role in intestinal immune development, homeostasis and inflammatory bowel diseases (IBD), however, our understanding of the underlying mechanisms by which it regulates these processes remains incomplete. Intestinal fibroblasts (iFB) are a heterogeneous population of tissue-resident cells increasingly recognized for their role in immune regulation. In preliminary studies, the host group and a collaborator found that human and mouse iFB express distinct arrays of microbial sensors and immune mediators and that iFB transcription is altered in germ-free mice. In my proposed project, I will combine state-of-the-art high dimensional flow cytometry, single cell (sc)RNA-seq, CITE-seq, spatial transcriptomics and bioinformatics analysis with animal models and analysis of human intestinal datasets to test the hypothesis that microbiome-iFB crosstalk plays a key role in intestinal immune system development, homeostasis and inflammation. Microbiome impact on iFB and intestinal immune system development will be assessed throughout the weaning period by treating mice with broad-spectrum antibiotics and/or antifungals. The importance of direct iFB-microbiome sensing for immune homeostasis and inflammation will be assessed as above as well as in dextran sulphate sodium (DSS)-induced colitis model in mice whose FB are deficient in either the Toll-like receptor signaling adaptor Myd88 or the C-type lectin receptor-Syk mediated antifungal response adaptor CARD9. Finally, translational aspects will be assessed through extensive bioinformatics analysis of iFB scRNA-seq datasets to map microbial sensor expression in human iFB subsets, evidence of downstream signaling through such sensors and their alterations in IBD. Collectively, this project uses a multi-systems approach to obtain novel insights into the importance of microbiome-iFB interactions in intestinal immune system homeostasis and disease with potential relevance for IBD management.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences chemical sciences inorganic chemistry alkali metals
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences basic medicine physiology homeostasis
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1165 KOBENHAVN
Denmark
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